Experimental and model-based approach to evaluate solvent effects on the solubility of the pharmaceutical artemisinin.

The separation and purification of plant-based Active Pharmaceutical Ingredients (API) from extracts is a crucial part in pharmaceutical process development. For the purification of the antimalarial drug component artemisinin (ARTE) from an Artemisia anna L. toluene extract, antisolvent crystallization is considered. Solubilities of ARTE in binary solvent mixtures of toluene and two potential antisolvents, n-heptane and ethanol, were determined at temperatures from 278.15 K to 313.15 K. The experimental work was supported by the application of various models, utilizing varying amounts of experimental input data. The goal was the identification of models that are able to predict solubilities in binary solvent mixtures sufficiently accurate and, thus, can help to reduce the experimental effort for future solvent screenings. In this study, we applied the PC-SAFT model both with and without fitting the binary interaction parameter kij between ARTE and the respective solvent, as well as the empirical Jouyban-Acree model. From the experiments, n-heptane demonstrated to be a promising antisolvent, while ethanol acted more as a cosolvent. All models tested were capable of distinguishing between effective and ineffective antisolvents. The purely predictive PC-SAFT model applied with kij = 0 exhibited the largest deviation from the experimental data. This was followed by the PC-SAFT model including fitted kij values, based on at least four experimental data points. The Jouyban-Acree model fitted the data most accurately. Its parametrization required a minimum of ten experimental data points.

A Contribution to the Solid State Forms of Bis(demethoxy)curcumin: Co-Crystal Screening and Characterization.

Bis(demethoxy)curcumin (BDMC) is one of the main active components found in turmeric. Major drawbacks for its usage are its low aqueous solubility, and the challenging separation from other curcuminoids present in turmeric. Co-crystallization can be applied to alter the physicochemical properties of BDMC in a desired manner. A co-crystal screening of BDMC with four hydroxybenzenes was carried out using four different methods of co-crystal production: crystallization from solution by slow solvent evaporation (SSE), and rapid solvent removal (RSR), liquid-assisted grinding (LAG), and crystallization from the melt phase. Two co-crystal phases of BDMC were obtained with pyrogallol (PYR), and hydroxyquinol (HYQ). PYR-BDMC co-crystals can be obtained only from the melt, while HYQ-BDMC co-crystals could also be produced by LAG. Both co-crystals possess an equimolar composition and reveal an incongruent melting behavior. Infrared spectroscopy demonstrated the presence of BDMC in the diketo form in the PYR co-crystals, while it is in a more stable keto-enol form in the HYQ co-crystals. Solubility measurements in ethanol and an ethanol-water mixture revealed an increase of solubility in the latter, but a slightly negative effect on ethanol solubility. These results are useful for a prospective development of crystallization-based separation processes of chemical similar substances through co-crystallization.